Homotopy continuation is an efficient tool for solving polynomial systems. Its efficiency relies on utilizing adaptive stepsize and adaptive precision path tracking, and endgames. In this article, we apply homotopy continuation to solve steady state problems of hyperbolic conservation laws. A third-order accurate finite difference weighted essentially non-oscillatory (WENO) scheme with Lax-Friedrichs flux splitting is utilized to derive the difference equation. This new approach is free of the CFL condition constraint. Extensive numerical examples in both scalar and system test problems in one and two dimensions demonstrate the efficiency and robustness of the new method.

Ligand-receptor binding and unbinding are fundamental biomolecular processes and particularly essential to drug efficacy. Environmental water fluctuations, however, impact the corresponding thermodynamics and kinetics and thereby challenge theoretical descriptions. Here, we devise a holistic, implicit-solvent, multi-method approach to predict the (un)binding kinetics for a generic ligand-pocket model. We use the variational implicit-solvent model (VISM) to calculate the solute-solvent interfacial structures and the corresponding free energies, and combine the VISM with the string method to obtain the minimum energy paths and transition states between the various metastable (“dry” and “wet”) hydration states. The resulting dry-wet transition rates are then used in a spatially-dependent multi-state continuous-time Markov chain Brownian dynamics simulations, and the related Fokker–Planck equation calculations, of the ligand stochastic motion, providing the mean first-passage times for binding and unbinding. We find the hydration transitions to significantly slow down the binding process, in semi-quantitative agreement with existing explicit-water simulations, but significantly accelerate the unbinding process. Moreover, our methods allow the characterization of non-equilibrium hydration states of pocket and ligand during the ligand movement, for which we find substantial memory and hysteresis effects for binding versus unbinding. Our study thus provides a significant step forward towards efficient, physics-based interpretation and predictions of the complex kinetics in realistic ligand-receptor systems.

In this paper, we give an integral approximation for the elliptic operators with anisotropic coecients on smooth manifold. Using the integral approximation, the elliptic equation is tranformed to an integral equation. The integral approximation preserves the symmetry and coercivity of the original elliptic operator. Based on these good properties, we prove the convergence between the solutions of the integral equation and the original elliptic equation.

The discrete fracture model (DFM) has been widely used in the simulation of fluid flow in fractured porous media. Traditional DFM uses the so-called hybrid-dimensional approach to treat fractures explicitly as low-dimensional entries (e.g. line entries in 2D media and face entries in 3D media) on the interfaces of matrix cells and then couple the matrix and fracture flow systems together based on the principle of superposition with the fracture thickness used as the dimensional homogeneity factor. Because of this methodology, DFM is considered to be limited on conforming meshes and thus may raise difficulties in generating high quality unstructured meshes due to the complexity of fracture's geometrical morphology. In this paper, we clarify that the DFM actually can be extended to non-conforming meshes without any essential changes. To show it clearly, we provide another perspective for DFM based on hybrid-dimensional representation of permeability tensor to describe fractures as one-dimensional line Dirac delta functions contained in permeability tensor. A finite element DFM scheme for single-phase flow on non-conforming meshes is then derived by applying Galerkin finite element method to it. Analytical analysis and numerical experiments show that our DFM automatically degenerates to the classical finite element DFM when the mesh is conforming with fractures. Moreover, the accuracy and efficiency of the model on non-conforming meshes are demonstrated by testing several benchmark problems. This model is also applicable to curved fracture with variable thickness.

Gibbs phenomenon is the particular manner how a global spectral approximation of a piecewise analytic function behaves at the jump discontinuity. The truncated spectral series has large oscillations near the jump, and the overshoot does not decay as the number of terms in the truncated series increases. There is therefore no convergence in the maximum norm, and convergence in smooth regions away from the discontinuity is also slow. In earlier work, a methodology is proposed to completely overcome this difficulty in the context of spectral collocation methods, resulting in the recovery of exponential accuracy from collocation point values of a piecewise analytic function. In this paper, we extend this methodology to handle spectral collocation methods for functions which are analytic in the open interval but have singularities at end-points. With this extension, we are able to obtain exponential accuracy from collocation point values of such functions. Similar to earlier work, the proof is constructive and uses the Gegenbauer polynomials $C^\lambda_n(x)$. The result implies that the Gibbs phenomenon can be overcome for smooth functions with endpoint singularities.